Meiotic maturation in amphibian oocytes involves a sequence of cell division events (e.g., breakdown of the nuclear membrane, condensation of chromosomes, spindle formation and cytokinesis) as well as activation of metabolic pathways in the cytoplasm and alterations of cell surface properties. The product of maturation is the unfertilized egg. Full-growth Xenopus oocytes can be removed from their follicles and matured in vitro in simple salt solutions, provided they are exposed to steroid hormones such as progesterone (cf. reviews by Schuetz, 1974, and Smith, 1975). Cytoplasmic intermediates in the progesterone stimulation of maturation have been detected: a small aliquot (2 to 5%) of cytoplasm from a maturing oocyte is withdrawn in a glass micropipet and injected into an unstimulated recipient oocyte, with the result that the recipient itself matures (Masui and Markert, 1971; Smith and Ecker, 1971). This "maturation-promoting-factor" (MPF) does not attenuate on 10-fold repeated serial transfer, indicating that it does not contain progesterone or a progesterone product, and is formed by an autoactivation mechanism. Thus, this system is particularly favorable to study of triggers of cell division and metabolic activation. We propose to isolate MPF and to study its formation and function during cell division. The finding that the factor is stabilized by phosphomonesters (R. Wallace) and by fluoride (K. Drury) suggests that it may be a phosphoprotein inactivated by phosphatases. Its activation may then involve kinases. Also, we know that many proteins become more heavily phosphorylated just prior to meiotic cell division and we believe that MPF acts by stimulating the phosphorylation of other proteins. We will continue to examine the variety of phosphoproteins formed in oocytes during maturation, and to identify the enzymes involved in these phosphorylation-dephosphorylation reactions. It is possible that meiotic cell division will involve cascades of enzyme activations based on protein phosphorylation, just as in the well-known metabolic activations of muscle and liver.